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ORIGINAL ARTICLE Rev Bras Cir Cardiovasc 2012;27(4):552-61

RBCCV 44205-1422DOI: 10.5935/1678-9741.20120097

Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failureAnastomose cavo-pulmonar associada ao suporte circulatório esquerdo comparada à assistência biventricular na falência cardíaca aguda

Luis Alberto Saraiva Santos1, Anderson Benício2, Ewaldo de Mattos Júnior3, Luiz Alberto Benvenutti4, Idágene Aparecida Cestari5, Noedir Antonio Groppo Stolf6, Luiz Felipe Pinho Moreira7

1. Federal University of Amazonas, Cardiac Physician Surgeron. Major author.

2. Heart Institute at Clinics Hospital of the University of São Paulo Medical School; PhD in Sciences (Thoracic and Cardiovascular Surgery) at University of São Paulo, Physician Collaborative Professor at University of São Paulo Medical School.

3. Heart Institute at Clinics Hospital of the University of São Paulo Medical School; Collaborative Researcher of the Bioengineering Department of the Heart Institute at Clinics Hospital of the University of São Paulo Medical School.

4. Heart Institute at Clinics Hospital of the University of São Paulo Medical School; Physician of the Pathology Service of the Heart Institute at Clinics Hospital of the University of São Paulo Medical School.

5. Heart Institute at Clinics Hospital of the University of São Paulo Medical School; Research and Development Director of the Bioengineering Department of the Heart Institute at Clinics Hospital of the University of São Paulo Medical School.

6 PhD in Sciences at University of São Paulo; Emeritus Professor of the Cardiovascular Surgery Department at Heart Institute at Clinics Hospital of the University of São Paulo Medical School.

7. Heart Institute at Clinics Hospital of the University of São Paulo Medical

School; Full Professor at University of São Paulo; Associate Professor of the Cardiovascular Surgery Discipline at University of São Paulo Medical School.

This study was carried out at Heart Institute at Clinics Hospital of the University of São Paulo Medical School, São Paulo, SP, Brazil.

Correspondence address:Luis Alberto Saraiva SantosAv. Dr. Enéas Carvalho de Aguiar, 44 – 2º andar, bloco 2, sala 13 – São Paulo, SP, Brazil – Zip code: 05403-000.E-mail: l_saraiva@ig.com.br

Support: Foundation for Research Support of the State of São Paulo (FAPESP).

Article received on May 8th, 2012Article accepted on September 5th, 2012

AbstractObjective: Right ventricular (RV) failure during left

ventricular assist device (LVAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavo-pulmonary anastomosis on LVAD performance and RV myocardial compromise in comparison with biventricular circulatory support, in a model of biventricular failure.

Methods: LVAD support was performed by centrifugal pump in 21 pigs with severe biventricular failure obtained by FV induction. Animals were randomized to be submitted to cavo-pulmonary anastomosis, to biventricular circulatory support or to control group. They were maintained under circulatory support and hemodynamic monitoring for 3h. Venous lactate and cytokines serum levels were also

obtained. Endocardium samples were analyzed by electronic microscopy.

Results: FV maintenance was responsible for acute LVAD impairment after 180 min in the control group. cavo-pulmonary anastomosis resulted in non-significant improvement of LVAD pump flow in relation to control group (+55±14 ml/kg/min, P=0.072), while animals under biventricular support maintained higher LVAD flow (+93±17 ml/kg/min, P=0.012). Mean arterial pressure remained constant only in biventricular group (P<0.001), which also presented decrease of right atrial and ventricular pressures. Similar increases in lactate and cytokines levels were observed in the three groups. Ultra-structural analysis documented low levels of myocardial swelling in the biventricular group (P=0.017).

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Rev Bras Cir Cardiovasc 2012;27(4):552-61Santos LAS, et al. - Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failure

Abbreviations, acronyms and symbols

LA Left atriumLVAD Left ventricular assist devices VF VentricularfibrillationEM Transmission electron microscopyOM Optical microscopyLAP Left atrial pressureMAP Mean arterial pressurePAP Pulmonary artery pressurePTFE ExpandedpolytetrafluoroethyleneCVP Central venous pressureRVP Right ventricular pressureRV Right ventricleLV Left ventricle

INTRODUCTION

Heart failure has been associated with poor prognosis and high morbidity and, despite optimal medical therapy, mortality remains unacceptably high, which justifiesthe search for alternative treatments. In this context, we can find mechanical circulatory support devices, whichprovide for this group of patients better quality and life expectancy [1-3].

One of the main complications of the implantation of left ventricular assist devices (LVAD) alone is the circulatory dysfunction of the right ventricle (RV), which

has an incidence varying between 13% and 44% [1,3,4]. Although controversial, most authors report that the institution of biventricular assistance should be performed as early as possible if the RV failure is hemodynamically important [4,5]. But with double of cannulation and pumps “sites", the adverse effects of this type of circulatory support increase[6].

Another alternative that has been suggested recently to acute right ventricular failure is the use of its surgical volume decompression volume through the cavopulmonary shunt [7,8]. The effectiveness of this procedure has been proven previously in experimental studies [9] and there

Conclusion: The concomitant use of cavo-pulmonary anastomosis during LVAD support in a pig model of severe biventricular failure resulted in non-significant improvement of hemodynamic performance and it did not effectively replace the use of biventricular support.

Descriptors: Heart-assist devices. Heart failure. Ventricular dysfunction, right. Heart bypass, right. Swine.

ResumoObjetivo: Este estudo avaliou o desempenho hemodinâmico

e as alterações miocárdicas decorrentes do emprego de dispositivos de assistência ventricular esquerda (DAVE), associado ou não à descompressão do ventrículo direito por meio de derivação cavo-pulmonar, sendo esses achados comparados ao emprego de assistência circulatória biventricular.

Métodos: Vinte e um suínos foram submetidos à indução de insuficiência cardíaca através de fibrilação ventricular, sendo a atividade circulatória mantida por DAVE durante 180 minutos. No grupo controle, foi apenas implantado o DAVE. No grupo derivação, além do DAVE foi realizada cirurgia de derivação cavo-pulmonar. No grupo biventricular, foi instituída assistência biventricular. Foram monitoradas as pressões intracavitárias por 3 horas de assistência e amostras do endocárdio dos dois ventrículos foram coletadas e analisadas à microscopia óptica e eletrônica.

Resultados: O lactato sérico foi significativamente menor no grupo biventricular (P=0,014). A diferença observada entre o fluxo do DAVE nos grupos derivação e controle (+55±14 ml/kg/min, P=0,072) não foi significativa, enquanto que o fluxo no grupo biventricular foi significativamente maior (+93±17 ml/kg/min, P=0,012) e se manteve estável durante o experimento. A pressão arterial média (PAM) se manteve constante apenas no grupo biventricular (P<0,001), que também apresentou diminuição significativa das pressões em câmaras direitas. Na análise ultraestrutural, notou-se menor presença edema miocárdico no ventrículo direito no grupo biventricular (P=0,017).

Conclusão: Os resultados apresentados demonstram que o desempenho hemodinâmico da assistência ventricular esquerda associada à derivação cavo-pulmonar, neste modelo experimental, não foi superior ao observado com a assistência de ventrículo esquerdo isolada e não substituiu a assistência biventricular de maneira efetiva.

Descritores: Coração auxiliar. Insuficiência cardíaca. Disfunção ventricular direita. derivação cardíaca direita. Suínos.

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is one report in the literature of patients who obtained clinical success of weaning from RV circulatory assist device, facilitated by the construction of cavopulmonary shunt when in use of biventricular assist device [8].

The aim of this study was to assess the hemodynamic performance and myocardial changes in the employment of LVAD, with or without RV decompression through cavopulmonary anastomosis in an experimental model of acute biventricular dysfunction in pigs and to compare these effects to those seen with the use of biventricular circulatory assistance. The influence of the types ofcirculatoryassistanceimposedoninflammatoryresponseand tissue perfusion of animals was also assessed.

METHODS

Twenty-one pigs, weighing between 25-35 kg, underwent induction of acute biventricular failure obtained from the onset of the rhythm of ventricular fibrillation (VF) by direct contact of a 12 volt electriccharge battery with the anterior heart wall. The circulatory activity was maintained by the institution of LVAD. This study was approved by the Research Ethics Committee of the institution under protocol (SDC-1649/00/10) and all animals underwent surgery according to the rules set in “Manual on the Care and Use of Laboratory Animals” and “European Convention on Animal Care”.

Protocol of animal experimentsThe animals were randomly divided into three groups

of seven pigs, called control group, bypass group and biventricular group. The surgical preparation was similar in the three groups. In the control group, LVAD was installed with centrifugal pump (Biopump, Medtronic, Inc.) with aortic cannulation, with angled 12 Fr wireframe arterial cannula (Medtronic, Inc.) and the tip of the left ventricle (LV), with single stage wireframe 24 Fr cannula (Medtronic, Inc.). In bypass group (Figure 1A), in addition to biopump on the left side of the heart was performed cavopulmonary anastomosis between the superior vena cava and the pulmonary artery using a non-wired No 16 expandedpolytetrafluoroethylene(PTFE)tube,whichwasmade before the circulatory assistance. In the biventricular group (Figure 1B), in addition to the left circulatory support, biopump has also been installed on the right side of the heart, through cannulation of the pulmonary artery and right atrial appendage, with tubes similar to those previously described.

Anesthetic and surgical preparationThe animals underwent general anesthesia with

ketamine (30 mg/kg im), midazolam (0.2 mg/kg, intravenously) and fentanyl (0.005 mg/kg, intravenously).

Additional doses of fentanyl were administered as needed. Intubation using 6.5 Fr cannula was performed and then a ventilator was introduced (Harvard ventilator 708, South Natik, MA, USA). Before the surgery, electrodes were placed on the animal, for continuous electrocardiogram recording.

A venous line (right femoral vein) was accessed for collection of serum samples, and if required, additional volume infused. For fluid infusion, a maximum of 100ml/kg was established in order to keep the central venous pressure (CVP) at normal values (10-14 mmHg). The temperature was obtained through a sensor inserted into the rectum, urinary output was measured by catheterization through cystostomy. Vasoactive drugs were not used in this protocol. An arterial line (right femoral artery) was obtained for monitoring of mean arterial pressure (MAP) and blood gas assessment and the right internal jugular vein was dissected for CVP monitoring.

The exposure of the heart was obtained through a median sternotomy and, after opening the pericardial sac, purse string sutures were performed in the left atrium (LA) and RV and micromanometers were inserted (5F, Model PC-350, Millar Instruments, Inc. Houston, USA) for continuous monitoring of intracavitary pressures. All sutures were performed in purses using prolene 4.0 wire, except the tip of the left ventricle, which was performed usingMersilene2.0polifilamentarwire.

After completion of the monitoring and cannulation of the animals, FV was induced, which was maintained by itself because it is not reversed by means of electrical defibrillation.Theflowwasmaintainedaslargeaspossible,taking as parameter the LA pressure, which had as its goal the value close to zero, thus connoting good blood return to the pulmonary territory and good LV drainage. In biventricular group, the begining of assistance at the right side of the heart was simultaneously to the left and in this flowwasmaintained at values lower than 20% than theleft sides.

Rev Bras Cir Cardiovasc 2012;27(4):552-61Santos LAS, et al. - Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failure

Fig. 1 - Schematic diagram of the surgical preparation. A: Bypass group B: biventricular group

A B

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Hemodinamic assessmentThe LV rhythm was maintained for 180 minutes and

during this period were recorded MAP, CVP, RV pressure (PVD) and left atrial pressure (LAP) in 30-minute intervals until the end of the protocol.

Evaluation of tissue perfusion and inflammatoryresponse

Changes in tissue perfusion and myocardial infarction were assessed before the procedure and every 30 minutes through collection of blood samples for analysis of blood gases, hematocrit, and lactate. Samples were collected for analysis of changes in the inflammatory response atthe time of initial preparation and subsequently every 60 minutes during the period of circulatory support. Serologic blood tests of TNF α, interleukin-1β and interleukin-6through specific antibody for pigs (Duo-Set, R & DSystems, Minneapolis, MN, USA) were performed.

Ultramicroscopic assessmentChanges of myocardial cells in the three groups were

assessed by optical microscopy (OM) and transmission electron microscopy (EM). Samples were taken at the RV free wall, in the interventricular septum and the LV free wall, obtained at the end of the experiment by removing the heart. The examiner was blind to the groups, after the result/report of the pathologist in charge, groups were revealedandthefinalresultofthisdatawasthenmade.

The samples were assessed by optical microscopy, being noted that they could be grouped into three distinct patterns of progressive gravity, as follows:

• Grade 0/+: Myocardium preserved or presenting small and scattered foci of recent necrosis of cardiomyocytes, characterized by cytoplasmic hypereosinophilia, contraction bands and nuclear pyknosis present only in the subendocardial region which presents no interstitial hemorrhage.

• Grade ++: Multiple foci of recent necrosis of cardiomyocytes in the subendocardial region, encompassing groups of cells, characterized by cytoplasmic hypereosinophilia, contraction bands and nuclear pyknosis, with or without small foci, sparse, of necrosis in mid-layer wall. It is the usual the presence of foci of hemorrhage in the subendocardium.

• Grade +++: Multiple foci of recent necrosis of cardiomyocytes in subendocardial and mid-mural region encompassing clusters of cells, characterized by cytoplasmic hypereosinophilia, contraction bands and nuclear pyknosis. Foci of hemorrhage in the subendocardium and crisp interstitial edema.

Under EM, the presence or absence of cellular swelling and swollen mitochondria, electron-dense bodies and lysis of myofilaments was assessed, and the first two beingconsidered lesions of mild to moderate intensity, and the last two, lesions of moderate to severe intensity. The

cellular edema was characterized by the presence of one or more areas of clear separation of organelles by edema. Themitochondrial swellingwasdefinedby thepresenceof irregular areas of vacuolization of the mitochondrial matrix, sometimes rupture of ridges present in several mitochondria.Theelectron-densebodiesweredefinedbythe presence of multiple electron-dense corpuscles in the mitochondrialmatrixand,ultimately,myofilaments lysiswas characterized by the presence of multiple areas of dissolutionofmyofilamentssarcomeres.

To avoid the appearance of post-mortem lesions that might distort the analysis of the material after removal of the heart, it was set maximum time of 15 minutes betweentheremovaloftheorganandfixingthematerialin glutaraldehyde.

Statistical AnalysisThe statistical analysis was performed using the

Graphpad Prism 5.2 software. The data were statistically assessed according to the type of distribution of variables. Parametric variables were expressed as mean ± standard error of the mean and were assessed by the two-tailed test of variance with repeated measures on the factor “time”, complemented by the Bonferroni t test. The variables of non-parametric distribution were expressed as medians andpercentiles,andwereassessedbyprofileanalysis.Thelevelofsignificancewassetat5%.

RESULTS

After the phase of protocol standardization, 21 full experiments were performed, seven in each group. The weight of the animals ranged from 25 to 32 kg, with a mean of 29 ± 3 kg, 30 ± 3 kg and 27 ± 4 kg in the control groups, bypass and biventricular, respectively. Comparable amount offluidwasadministeredinthethreegroups.Thevaluesof arterial blood gases, hematocrit and hemoglobin were similar between groups. Serum lactatewas significantlylower in biventricular group (Table 1).

Hemodynamic performance assessmentThe hemodynamic data are shown in Table 2. LVAD

flows observed were similar in the control groups andcavopulmonarybypass,whileflowinbiventriculargroupwas significantly higher throughout the experiment(Figure 2).

The study of the pressure behavior in the left circulation has shown the maintenance of normal levels of MAP throughout the period of circulatory assistance only in the biventricular group, while the other groups showed a progressive decrease of this parameter. This drop, however, was not statistically significant and shows satisfactorymaintenance of levels by the end of the experiments in

Rev Bras Cir Cardiovasc 2012;27(4):552-61Santos LAS, et al. - Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failure

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the three groups studied (Figure 3A). The LVP assessment demonstrated effective performance of left ventricular assist in all experiments (Figure 3B).

Regarding the behavior of the pressure in the right chambers, we observed the existence of lower values only in the biventricular group, being observed similar values

Table 2. Hemodynamic results.

MAPControlBypassBiventricular

CVPControlBypassBiventricular

LAPControlBypassBiventricular

RVPControlBypassBiventricular

Pre

51.99 ± 7.5358.95 ± 9.8158.19 ± 5.03

5.20 ± 1.375.60 ± 2.995.20 ± 1.13

7.78 ± 2.848.35 ± 2.598.15 ± 1.98

12.14 ± 2.6311.09 ± 3.689.77 ± 3.45

30’

42.66 ± 14.4945.49 ± 12.2153.80 ± 11.13

10.68 ± 2.9813.19 ± 5.359.03 ± 2.14

3.09 ± 3.252.57 ± 3.132.87 ± 2.96

13.89 ± 5.4513.31 ± 6.0711.66 ± 2.74

60’

38.93 ± 15.2443.51 ± 10.8955.03 ± 11.97

10.97 ± 1.9413.54 ± 4.398.55 ± 3.12

2.71 ± 3.333.45 ± 3.232.50 ± 1.38

14.84 ± 5.8414.01 ± 4.9412.09 ± 2.69

90’

36.97 ± 15.0244.66 ± 13.4952.55 ± 14.34

11.21 ± 2.0413.48 ± 3.148.08 ± 3.28

1.39 ± 1.863.84 ± 3.443.58 ± 2.16

13.75 ± 5.6214.12 ± 3.7912.51 ± 2.13

120’

37.63 ± 14.1242.58 ± 13.8153.24 ± 11.43

10.88 ± 2.4413.26 ± 3.0410.37 ± 2.42

2.44 ± 2.343.21 ± 3.664.13 ± 2.36

15.32 ± 6.3814.01 ± 3.6212.32 ± 2.05

Control = control group; Bypass = bypass group; Biventricular = biventricular group, MAP = mean arterial pressure, CVP = central venous pressure; LAP = left atrial pressure; RVP = right ventricular pressure.

150’

3607 ± 15.8742.07 ± 12.9151.43 ± 12.68

11.08 ± 2.7213.39 ± 2.859.60 ± 3.92

2.61 ± 2.773.01 ± 3.053.42 ± 2.74

15.82 ± 5.2814.00 ± 3.2012.35 ± 2.05

180’

32.52 ± 15.6142.02 ± 11.9251.12 ± 12.84

10.37 ± 3.0013.48 ± 2.988.89 ± 3.71

2.87 ± 2.841.72 ± 2.603.29 ± 3.02

16.74 ± 5.6414.02 ± 3.4711.54 ± 2.10

Table 1. Serum lactate results.

ControlBypassBiventricular

Pre0.81±0.061.20±0.500.72±0.34

1 hour2.47±2.063.55±3.591.60±1.31

2 hours3.31±2.904.34±4.111.75±1.36

3 hours3.62±2.875.21±4.761.98±1.61

P=0.014Lactate

Control = control group; Bypass = bypass group, Biventricular = biventricular group.

Rev Bras Cir Cardiovasc 2012;27(4):552-61Santos LAS, et al. - Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failure

Fig. 2 - Ventricular assist device flow.Left Ventricular Assist Device Flow (LVAD). Values in mean ± standard error of the mean.Difference between groups: P = 0.012

of pressure in the superior vena cava and right ventricle of the animals in the control group and cavopulmonary bypass group (Figures 4A and 4B).

Inflammatory response assessmentThe assessment results of the inflammatory response

through serum cytokine dosage are presented as medians and percentiles. Although there was a trend to higher levels of TNFa with maintaining circulatory assistance for longer periods in the biventricular group, this difference was not significant froma statistical standpoint.Therewere alsonosignificantdifferencesbetweenthegroupsinrelationtotheinterleukins6and1βvalues(Figure5).

Assessment of changes in myocardial cellsTable 3 shows the changes under OM observed in the

groups.Therewerenosignificantdifferencesinthedegreeofdamageofmyocardialfibers in theLVandRV,whilethe biventricular group showed fewer changes considered more severe in the septum.

The results of the changes observed under EM are

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shown in Table 4. We can observe the occurrence of more cases with the presence of cellular edema and mitochondrial edema in the control group and cavopulmonary bypass group in relation to the biventricular group in the RV free

Rev Bras Cir Cardiovasc 2012;27(4):552-61Santos LAS, et al. - Cavo-pulmonary anastomosis associated with left ventricular in comparison with biventricular circulatory support in acute heart failure

Fig. 5 - Markers of the inflammatory response

Fig. 4A - Right Ventricular Pressure (RVP) Values in mean ± standard error of the mean. Difference between groups: P = 0.3414B. Central Venous Pressure (CVP) Values in mean ± standard error of the mean.Difference between groups: P=0.043

4A 4B

Fig 3 - Pressures of the left side of the heart.3A. Mean Arterial Pressure (MAP); Values in mean ± standard error of the mean. 3B - Left Atrium Pressure (LAP); Values in mean ± standard error of the mean. Difference between groups: P=0.074

3A 3B

wall. The increased presence of cellular edema in the interventricular septum also observed in the control group andcavopulmonarybypassgroup,butwasnotsignificantfrom a statistical standpoint.

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Cellular edemaRight ventricleSeptumLeft ventricle

Mitochondrial edemaRight ventricleSeptumLeft ventricle

Electron-dense bodiesRight ventricleSeptumLeft ventricle

LiseMyofibrillarRight ventricleSeptumLeft ventricle

Table 4. Changes in electron microscopy.Control

6 (7)6 (7)2 (7)

2 (7)4 (7)2 (7)

0 (7)2 (7)1 (7)

0 (7)2 (7)0 (7)

Bypass

5 (7)5 (7)5 (7)

4 (7)2 (7)2 (7)

1 (7)0 (7)3 (7)

0 (7)0 (7)3 (7)

Biventricular

1 (7)2 (7)5 (7)

0 (7)1 (7)4 (7)

1 (7)1 (7)4 (7)

1 (7)1 (7)2 (7)

Numbers indicate the positive cases (total cases)

P=0.017P=0.072P=0.173

P=0.061P=0.223P=0.446

P=0.575P=0.311P=0.243

P=0.349P=0.311P=0.159

Table 3. Results of optical microscopy.

Cellular changes pattern

Right ventricle

Septum

Left ventricle

Control

Grade 0/+ (5)Grade ++ (1)

Grade +++ (1)Grade 0/+ (3)Grade ++ (0)

Grade +++ (4)Grade 0/+ (1)Grade ++ (2)

Grade +++ (4)

Bypass

Grau 0/+ (4)Grade ++ (1)

Grade +++ (2)Grade 0/+ (1)Grade ++ (3)

Grade +++ (3)Grade 0/+ (1)Grade ++ (2)

Grade +++ (4)

Biventricular

Grade 0/+ (4)Grade ++ (2)

Grade +++ (1)Grade 0/+ (5)Grade ++ (0)

Grade +++ (2)Grade 0/+ (3)Grade ++ (0)

Grade +++ (4)Numbers indicate the positive cases (total cases)

P = 0.885

P = 0.053

P = 0.462

DISCUSSION

The RV failure occurs in 13% to 44% of patients undergoing implantation of LVAD devices alone, being the major cause of postoperative mortality of this procedure [1]. The use of uni- or biventricular assistance is the key to therapeutic success in treating patients with heart failure [10,11].However,itisdifficulttopredictwhopatientsareat increased risk of developing RV failure, because there is no consensus on criteria for preoperative risk among these studies [10-12].

Cavopulmonary anastomosis seems to be able to increase the effective pulmonary flow because volumetricallydecompresses the RV, restoring its geometric shape [7,13]. There are clinical [8] and experimental [7,9] suggestions in the literature that the partial exclusion of the RV is beneficialinthetreatmentofrightfailure.

Danton et al. [9] demonstrated in an experimental model of acute myocardial infarction in pigs, the effectiveness of cavopulmonary anastomosis in RV decompression volume. Succi et al. [7] succeeded in demonstrating an experimental model in dogs that cavopulmonary

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anastomosis is able to provide adequate support to the RV, when combined with mechanical assistance to LV in biventricular failure. However, despite hemodynamic improvement evidenced in this study, the authors received major criticism for certain technical aspects, as the local drainage of the left system, which was performed by LA, the short time in which the animal was kept in failure (90 minutes), and questions about the choice of the use of continuousflowpumpsandnon-pulsatileflow.

In the present study, when the cavopulmonary anastomosis associated to LAVD was compared to LVAD alone, unlike the previous study, there was no significant hemodynamic improvement with the use ofthe method as compared to control, both being lower than the biventricular circulatory assistance. Perhaps technical changes in the performance of the cavopulmonary anastomosis, as the anastomosis in the pulmonary artery trunk and the use of synthetic tube instead of autologous tissue,haveinfluencedresults.

Classic cavopulmonary anastomosis already clinically demonstrated efficacy in the presence of circulatorysupport in a situation in which it was helpful in the case of a patient with biventricular assist weaning with the right circulatory support facilitated by such surgery [8]. The option of making the cavopulmonary anastomosis was modified motivated by technical difficulties inperforming the classic form. As a result we chose to use the synthetic tube (PTFE No. 16), which, despite having adequate caliber, it is speculated that it has less complacency than the native tissue vena cava. Danton et al. [9] performed an experimental study of acute RV failure and obtained satisfactory decompression of this chamber, when performing cavopulmonary anastomosis using modified autologous inferior vena cava, demonstratingthe effectiveness of the method to decompress the RV presenting acute failure.

Another factor to be considered is again the time, because even though the animals have been exposed in this study to VF twice as long compared to the protocol used previously in the study by Succi et al. [7], there was no significanthemodynamic deterioration during the period of observation, and so maybe cavopulmonary anastomosis decompression hasnotshowntheexpectedhemodynamicefficacy.

It should also be highlighted the question, in the present study, the local chosen for left drainage was the LV, which is set as the default location for this type of assistance [14], perhaps contributing to the less pronounced hemodynamic failure observed in this model. The use of pigs in this experiment, insteadofdogs,directly influenced thefinaloutcome, because they are different species with different behavioral and physiological responses to trauma.

There are numerous causes of failure of Glenn' surgery, including variations in pulmonary artery pressure, and high

pulmonary vascular resistance among the major causes. In this sense there are recommendations, not consensual, to perform such surgery only in cases where the pulmonary artery pressure (PAP) is less than 18 mmHg, and ideally less than 15 mmHg, with pulmonary vascular resistance less than 2.0 Wood units [ 13]. In the present study, we used young animals without previous diseases, a fact that makes it unlikely that they have some kind of native pulmonary vascular disease. Furthermore, PAP was measured prior in all animals, which was within normal limits.

Moreover, it is known that the biventricular assistance is effective in decompressing the dilated RV, when it enters into failure and there are suggestions in the literature that such behavior should be instituted as early as possible in order to avoid irreversible damage to target organs [14,15]. However, despite the observed hemodynamic improvement, it is known that this type of assistance, despite the technological advances offered by new devices, it still remains high incidence of complications [7,14,16]. To that end, numerous studies are listed in an attempt to elucidate the criteria that could predict which patients are at higher risk of developing RV failure after the LVAD institution.

In the experimental model presented here, the circulatory support was instituted by centrifugal pump. This system is widely available in a specialized environment, has low cost, is easy to handle and there are several reports of successful clinical use in the literature. However, there are guidelines that its use should not be extended, because this type of assistance mechanism exacerbates theinflammatoryresponseovertime[17].Thisstatementiscontroversialandsomestudiesclaimthatthelowflowresulting from circulatory collapse, common at the time of institution of this kind of assistance would be primarily responsible for this exacerbation, and so successfully demonstrated that, after normalization of tissue perfusion obtainedwithassistance,thereisdecreaseininflammatorycytokines[18].Thisobservationcorroboratesthefindingsofthisprotocol,whichshowednosignificantincreaseininflammatorycytokines studied thusassuming that therewas adequate tissue perfusion during the experiment.

Regarding the assessment of myocardial cells, it has been demonstrated in experimental model of infarction in pigs that irreversible ultrastructural lesions begin in just 15 minutes and that in 30 minutes, mitochondrial destruction occurs, thus characterizing cell death [19]. Moreover, it is widely accepted that during acute myocardial infarction myocardial ischemia propagates from subendocardial region to epicardial region, a phenomenon called “Wavefront Phenomenon” [20]. It has also been shown the occurrence in dilated cardiomyopathy, early ultrastructural changes, characterized by degeneration of mitochondrial andmyofibrillarlysis[21].

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Based on these concepts, samples collected from the subendocardial region of the RV, LV and septum were assessed under OM and EM. Under OM and EM, we observed decrease in the occurrence of cellular and mitochondrial swelling in the RV in the biventricular group. This fact can be explained by adequate drainage provided with such assistance, which decreases the chance of endocardial injury by increase of intracavity voltage.

The outcomes demonstrated in this study are subject to several limitations. Again, the short observation period can be considered the major limitation. Moreover, technical problems such as the assistance provided by centrifugal pumps and cannulae used in the experiments that were not manufactured for such purpose, may be greatly influenced the quality of the circulatory assist providedin the model. It is woth emphasizin that these are closer to the reality experienced by most specialized centers in our country. Functional evaluation methods, such as echocardiography, have their effective in assessing cardiac function in pigs proven in the literature and would be useful in this protocol [22]. In addition to these methods, it hasrecentlybeendemonstratedthatpulsatileflowpumpsareaseffectiveasthecontinuousflowpumpsinrelationto hemodynamic performance, but with less activation of part of the inflammatory system [23].Another factorof great importance was the direct measurement of PAP, through which it would be possible to calculate pulmonary vascularresistance,whichmayhaveinfluencedtheproperfunctioning of the cavopulmonary shunt.

The results of this study demonstrated that RV volumetric decompression through the cavopulmonary anastomosismodifiedinacutebiventricularfailure,whileusing LVAD mechanisms alone, was not superior than that observed by the institution of biventricular assistance and therefore should not be used as routine in surgical practice. However, more studies are needed to define the use ofbiventricular assist as standard procedure in the presence of acute RV failure.

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